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Liver Failure, Acute on ChronicPhase 1NCT05881668

MSC-EV in Acute-on-Chronic Liver Failure After Liver Transplantation

A Phase 1 study testing MSC-EV in people with Liver Failure, Acute on Chronic, run by Third Affiliated Hospital, Sun Yat-Sen University at 1 site in China.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Acute-on-chronic liver failure refers to a liver failure syndrome in which some patients with chronic liver disease with relatively stable liver function suffer from acute liver decompensation and liver failure due to the effects of various acute injury factors. Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Liver Failure, Acute on Chronic
What is being tested?
MSC-EV
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteChina
Study dates
30 Sep 2023to 30 Apr 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • aged 18-60 years;
  • Acute on chronic liver failure-which is characterized by acute hepatic insult manifesting as jaundice (serum total bilirubin [TBil] ≥ 10×ULN umol/L) and coagulopathy (international normalized ratio [INR] ≥ 1.5 or prothrombin activity < 40%), complicated within 4 weeks by ascites and/or encephalopathy as determined by physical examination, in patients with previously diagnosed or undiagnosed chronic liver disease; Requiring liver transplantation due to acute on chronic liver failure;
  • Obtain the patients' consent after informing patients of the purpose and method of the clinical trial;

Who cannot join

  • Past history of malignant disease
  • Active uncontrolled infection;
  • Combined transplantation
  • EBV-negative;
  • HIV or HCV positive;
  • Retransplantation;

Trial locations and contacts

1 site in 1 country.

China1 site

  • Third Affiliated Hospital, Sun Yat-Sen University

    Guangzhou, Guangdong, 510630

Other trials in China

About this study

Official title: Mesenchymal Stem Cells-Derived Extracellular Vesicles (MSC-EV) in Acute-on-Chronic Liver Failure After Liver Transplantationa：a Prospective, Randomized, Controlled Clinical Study

Acute-on-chronic liver failure refers to a liver failure syndrome in which some patients with chronic liver disease with relatively stable liver function suffer from acute liver decompensation and liver failure due to the effects of various acute injury factors. Liver transplantation is the only curative treatment for this type of end-stage liver disease. The potential of MSCs to repair or regenerate damaged tissue and suppress immune responses makes them promising in the treatment of liver diseases, especially in the field of liver transplantation. Many studies have shown that MSC-based therapies can reduce the symptoms of liver disease due to their paracrine effects. Therefore, compared to the cells they derive from, mesenchymal stem cells-derived extracellular vesicles (MSC-EV) are gradually gaining attention for their enhanced safety, as they do not replicate or cause microvascular embolism, and can be easily stored without losing their properties. It represents a novel and effective cell-free therapeutic agent as alternative to cell-based therapies for liver diseases, and liver failure was also concerned. This study was designed to evaluate the safety and tolerability of MSC-EV in acute-on-chronic liver failure after liver transplantation.

Read the detailed description

In the MSC-EV group (experimental group), 15 patients will receive a single injection of MSC-EV after their first liver transplantation. In the non-MSC-EV group (control group), 15 patients will not receive MSC-EV therapy after their first liver transplantation.

The outcome of the experimental group will be compared with that of similar control patients undergoing liver transplantation but who will not receive MSC-EV. Both of the two groups will receive standard immunosuppressive therapy( a regimen based on tacrolimus (TAC), mycophenolate mofetyl (MMF) and steroids). Patients participated in the experimental cohort will be infused with a single dose of 10 E10 MSC-EV particles per 100ml, at an appropriate time during the first 1-5 days after transplantation.

Being tested
MSC-EV
Keywords
MSC-EV, Acute-on-chronic liver failure, Liver transplantation
Medical subject headings
Acute-On-Chronic Liver Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MSC-EVBiological

    10 E10 MSC-EV particles per 100ml for a single dose. No prior HLA matching between MSC donors and recipients or liver donors

Study groups in NCT05881668
Study groupRoleWhat they receive
MSC-EV groupExperimentalAfter liver transplantation, on the basis of postoperative standard treatment (anti-infection treatment, immunosuppressive treatment, nutritional support treatment, etc.), an additional injection of MSC-EV will be received between the 1st and 5th days after transplantation
Receives: Biological: MSC-EV
Non-MSC-EV groupNo interventionAfter liver transplantation, patients will receive postoperative standard treatment (anti-infection treatment, immunosuppressive treatment, nutritional support treatment, etc.)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with MSC-EV infusion-related toxicity as assessed by CTCAE v4.0.

    Incidence, timing and severity of any clinical complication related to MSC-EV infusion, such as tympanic body temperature, heart rate, mean arterial blood pressure and allergy, as assessed by CTCAE v4.0 .

    Measured: 24 hours after injection

  2. Aspartate aminotransferase (AST)

    Collect clinical results reflecting liver function

    Measured: 6 months after transplantation

  3. Alanine aminotransferase (ALT)

    Collect clinical results reflecting liver function

    Measured: 6 months after transplantation

  4. Bilirubin level

    Collect clinical results reflecting liver function

    Measured: 6 months after transplantation

  5. International normalized ratio (INR)

    Collect clinical results reflecting liver function

    Measured: 6 months after transplantation

  6. carbohydrate Compound antigen (GGT) level

    Collect clinical results reflecting liver function

    Measured: 6 months after transplantation

  7. Adverse events

    Any adverse events which may related to MSC-EV infusion

    Measured: 6 months

Secondary outcomes (3)

  1. Number of survived patients at 1 year after liver transplantation, according to the follow-up results.

    Patients who are surviving, as assessed by outpatient or telephone follow-up, at 1 year after liver transplantation

    Measured: 12 months

  2. Number of survived grafts at 1 year after liver transplantation, according to the follow-up results.

    Surviving patients with primary and functional grafts, as assessed by outpatient or telephone follow-up, at 1 year after liver transplantation.

    Measured: 12 months

  3. Recipient's immune function, as assessed by analysis of immune cell subsets from biopsy or blood samples ,at months 1-6 after liver transplantation.

    A series of immune cell subsets will be analyzed, including T cells (CD3+), CD4+ T cells (CD3+ CD4+ lymphocytes), CD8+ T cells (CD3+ CD8+ lymphocytes), naïve CD4+ T cells (CD4+ CD45RAhigh lymphocytes), memory CD4+ T cells (CD4+ CD45RO+ lymphocytes), natural killer (NK) cells (CD3- CD56+ lymphocytes), as well as B cells (CD19+ lymphocytes)

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 May 2023
  2. Study start30 Sep 2023 (estimated)
  3. Primary completion30 Sep 2024 (estimated)
  4. Study completion30 Apr 2025 (estimated)

Why it stopped: The supply of msc-ev has been delayed and approval by the Ethics committee will take some time.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05881668
Sponsor's protocol ID
MSC-EV of ThirdSunYatSen
Status last verified
Oct 2023
First submitted
8 May 2023
Last updated
12 Oct 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Detry O, Vandermeulen M, Delbouille MH, Somja J, Bletard N, Briquet A, Lechanteur C, Giet O, Baudoux E, Hannon M, Baron F, Beguin Y. Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study. J Hepatol. 2017 Jul;67(1):47-55. doi: 10.1016/j.jhep.2017.03.001. Epub 2017 Mar 9.

    PubMed 28284916

  • Lin BL, Chen JF, Qiu WH, Wang KW, Xie DY, Chen XY, Liu QL, Peng L, Li JG, Mei YY, Weng WZ, Peng YW, Cao HJ, Xie JQ, Xie SB, Xiang AP, Gao ZL. Allogeneic bone marrow-derived mesenchymal stromal cells for hepatitis B virus-related acute-on-chronic liver failure: A randomized controlled trial. Hepatology. 2017 Jul;66(1):209-219. doi: 10.1002/hep.29189. Epub 2017 May 27.

    PubMed 28370357

  • Psaraki A, Ntari L, Karakostas C, Korrou-Karava D, Roubelakis MG. Extracellular vesicles derived from mesenchymal stem/stromal cells: The regenerative impact in liver diseases. Hepatology. 2022 Jun;75(6):1590-1603. doi: 10.1002/hep.32129. Epub 2021 Nov 27.

    PubMed 34449901

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MSC-EV in people with Liver Failure, Acute on Chronic, run by Third Affiliated Hospital, Sun Yat-Sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 12 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with MSC-EV infusion-related toxicity as assessed by CTCAE v4.0. (time frame: 24 hours after injection). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05881668, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2023.

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